Mutants of the Rb and p53 genes and uses thereof

Abstract

The present invention provides mutants of the Rb gene and methods utilizing these mutants. Along with mutated Rb genes, the present invention provides plasmids containing a mutated Rb gene. In addition, the present invention provides cells transfected with the plasmids of the present invention. Moreover, the present invention provides for methods of inhibiting pathophysiological cell proliferation.

What is claimed is:  
     
       1. A method of inhibiting pathological proliferation of a cell comprising administration of a DNA molecule comprising a synthetic mutated Rb gene encoding a mutated functionally active retinoblastoma protein, wherein said Rb gene is mutated by changing nucleotides that code for amino acids necessary for phosphorylation induced inactivation of Rb function. 
     
     
       2. The method of claim  1 , wherein said gene is mutated by changing the nucleotide sequence that encodes amino acids in conserved homology regions of the Rb gene. 
     
     
       3. The method of claim  2 , wherein said conserved homology region of the Rb gene is selected from the group consisting of P1 (SEQ ID NO: 4), P3 (SEQ ID NO: 6) and P5 (SEQ ID NO: 8). 
     
     
       4. The method of claim  3 , wherein said gene encodes an amino acid sequence selected from the group consisting of the sequences shown in Seq. ID. Nos: 1 and 2. 
     
     
       5. The method of claim  1 , wherein said gene is mutated by changing the nucleotide sequence that encodes amino acids in phosphorylation sites of the Rb protein. 
     
     
       6. The method of claim  5 , wherein said phosphorylation sites are selected from the group consisting of one or more of T005, S230, S249, T252, T356, T373, S567, S608, S612, T773, S780, S788, S795, S807, S811, T821 and T826. 
     
     
       7. The method of claim  6 , wherein said phosphorylation sites are selected from the group consisting of one or more of T356, S788, S807, S811 and T821.